反应详情

5-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 6.2, 500 mg, 1.264 mmol), (S)-beta-prolinol hydrochloride (226 mg, 1.643 mmol), DIPEA (662 μL, 3.79 mmol) and iPrOH (1.945 mL) were added to a MW vial and subjected to MW irradiation at 140° C. for 60 min. The solvent was evaporated off under reduced pressure and the residue was treated with aq. 0.5 M HCl (20 mL) and extracted with EtOAc. The combined extracts were washed with 0.5 M HCl (10 mL) and water, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the product which was triturated with cyclohexane, filtered and dried to afford the title compound as a white solid. UPLC-MS (Condition 1) tR=2.76 min, m/z=460.0/462.0 [M+H]+, m/z=458.0/460.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.59-1.76 (m, 1H) 1.92-2.04 (m, 1H) 2.26-2.44 (m, 1H) 3.37-3.50 (m, 2H) 3.56 (dd, J=11.00, 7.34 Hz, 1H) 3.67-3.85 (m, 3H) 4.71 (br. s, 1H) 7.35 (d, J=8.56 Hz, 2H) 7.85 (d, 1H) 8.34 (d, J=1.96 Hz, 1H) 8.68 (d, J=1.96 Hz, 1H) 10.21 (s, 1H).

1. customsubjected to MW irradiation at 140° C. for 60 min
2. customThe solvent was evaporated off under reduced pressure
3. additionthe residue was treated with aq. 0.5 M HCl (20 mL)
4. extractionextracted with EtOAc
5. washThe combined extracts were washed with 0.5 M HCl (10 mL) and water
6. dry with materialdried over MgSO4
7. customthe solvent was evaporated off under reduced pressure
8. customto give the product which
9. customwas triturated with cyclohexane
10. filtrationfiltered
11. customdried